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Developmental neurotoxicity of methylmercury and methylazoxymethanol: body weight, motor activity and brain damage combined.

de Groot-D; Moerkens-M; Janskin-R; Otto-M; van de Horst-L; Bos-Kuijpers-M; Waalkens-I; O'Callaghan-J; Gundersen-HJ; Kaufmann-W; Lammers-J; Pakkenberg-B
Neurotoxicology 2006 Sep; 27(5):913
Motor activity was studied in rats, prenatally exposed to methyl mercury (MeHg) or methylazoxy methanol (MAM) (five dose levels each) on PN 13, 17, 21 and 62, as required by the EPA guideline for developmental neurotoxicity (DNT) testing (OPPTS 870.6300). Neuropathology was studied on PN 22 and PN 62. Both neurotoxicants are known to affect brain morphology during development. MeHg, however, primarily causes systemic toxicity. The results of the motor activity profiles of both compounds were mutually compared and considered in view of body weight changes and brain damage. Statistically significant effects on motor activity per test age were not observed either for MAM or MeHg, males or females. However, in the top doseMAMgroup, the time pattern of motor activity differed from controls: hypo-activity on PN 13 and hyper-activity particularly on PN 21. In MeHg-exposed F1-rats, the time pattern of motor activity also differed from that in the top-dose MAM group and showed higher activity than controls on PN17 and lower activity on PN 21. Brain morphology showed considerable effects of MAM in the forebrain including also a loss of hippocampal CA1 neurons. Effects on cerebellum were not found for MAM. Body weight changes were the same for MAMand MeHg and did not explain the differences in the time pattern of motor activity between the two model compounds. Relating the motor activity results with the neuropathology findings it was concluded that the hyperactivity on PN 21 (MAM) suggested a loss of spatial memory due to observed neuron loss in the hippocampal CA1 region, rather than motor impairment. Neuron loss in the cerebellum and changes found in volume of regions in cerebellum and brain stem (MeHg) most likely account for motor impairment. The results of the present study illustrate the relevance of combining functional and morphological data when considering their impact with regard to developmental neurotoxicity.
Neurological-diseases; Neurological-reactions; Neurological-system; Chemoreceptors; Brain-disorders; Brain-damage; Brain-electrical-activity; Brain-function; Animal-studies; Motion-studies
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